Institute for Integrative Toxicology, Michigan State University, Lansing East, MI, 48824, United States.
Institute for Integrative Toxicology, Michigan State University, Lansing East, MI, 48824, United States; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, 48824, United States.
Toxicology. 2018 Mar 1;396-397:46-53. doi: 10.1016/j.tox.2018.01.004. Epub 2018 Feb 8.
Bisphenol A (BPA) is extensively used in manufacturing of a broad range of consumer products worldwide. Due to its widespread use, human exposure to BPA is virtually ubiquitous. Broad human exposure coupled with a large scientific literature describing estrogenic activity of BPA in animals has raised public health concerns. To comprehensively evaluate the health effects of BPA exposure, a chronic toxicity study using a wide-range of BPA doses (2.5-25000 μg/kg bw/day) was conducted jointly by the NTP, thirteen NIEHS-supported grantees, and the FDA, which is called the Consortium Linking Academic and Regulatory Insights on Toxicity of BPA (CLARITY-BPA). As a participant in the CLARITY-BPA project, the objective of the current study was to evaluate the effects of chronic BPA exposure in Sprague-Dawley rats on the relative number and proportion of defined leukocyte populations in the spleen and the thymus. Toward this end, lymphoid tissues from a total of 641 rats were assayed after being continuously dosed with BPA or controls for up to one year. To comprehensively evaluate the effects of BPA on leukocyte compositions, extensive endpoints that cover major populations of leukocytes were assessed, including B cells, T cells, NK cells, granulocytes, monocytes, macrophages and dendritic cells. In total, of the 530 measurements in BPA-treated rats, 10 measurements were statistically different from vehicle controls and were mainly associated with either the macrophage or dendritic cell populations. Most, if not all, of these alterations were found to be transient with no persistent trend over the one-year time period. In addition, the observed BPA-associated alterations were mostly moderate in magnitude and not dose-dependent. Due to the aforementioned, it is unlikely that the observed BPA-mediated changes alone would adversely affect immune competence.
双酚 A（BPA）在全球范围内广泛用于制造各种消费品。由于其广泛使用，人类接触 BPA 几乎无处不在。广泛的人类接触，加上大量描述 BPA 在动物体内具有雌激素活性的科学文献，引起了公众健康的关注。为了全面评估 BPA 暴露对健康的影响，NTP、13 个 NIEHS 资助的研究机构和 FDA 联合进行了一项使用广泛 BPA 剂量（2.5-25000μg/kg·bw/天）的慢性毒性研究，称为 BPA 毒性的学术和监管综合评估联盟（CLARITY-BPA）。作为 CLARITY-BPA 项目的参与者，本研究的目的是评估慢性 BPA 暴露对 Sprague-Dawley 大鼠脾脏和胸腺中定义的白细胞群体的相对数量和比例的影响。为此，共对 641 只连续接受 BPA 或对照处理长达一年的大鼠的淋巴组织进行了检测。为了全面评估 BPA 对白细胞组成的影响，评估了涵盖白细胞主要群体的广泛终点，包括 B 细胞、T 细胞、NK 细胞、粒细胞、单核细胞、巨噬细胞和树突状细胞。在 BPA 处理的大鼠的 530 个测量值中，有 10 个测量值与载体对照有统计学差异，主要与巨噬细胞或树突状细胞群体有关。这些改变中的大多数（如果不是全部）是短暂的，在一年的时间内没有持续的趋势。此外，观察到的与 BPA 相关的改变大多是中等程度的，并且与剂量无关。由于上述原因，观察到的 BPA 介导的变化不太可能单独对免疫能力产生不利影响。
